A preliminary report assessing the feasibility and effectiveness of amniotic bladder therapy in patients with chronic radiation cystitis.

INTRODUCTION: Chronic radiation cystitis (CRC) can develop between 6 months and 20 years after radiation therapy that presents with symptoms of urinary frequency, urgency, bladder pain, and nocturia. Amniotic membrane (AM) is known to contain pro-regenerative properties and could thereby be a potential therapeutic modality for radiation-induced tissue injury of the bladder. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received amniotic bladder therapy (ABT) comprised of intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey) were repeated at preop and 2, 4, 8 and 12 weeks post-injection. RESULTS: Five consecutive female patients aged 64.4 ± 20.1 years with a median CRC disease duration of 10 years were included. After ABT, BPIC-SS scores improved from baseline to 12 weeks (36.6 ± 1.1 to 12.6 ± 3.1) and this was associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. One patient had an acute urinary tract infection at 2 weeks but was successfully treated with oral antibiotics. No other adverse events related to micronized AM injections were observed. Uroflow assessments showed increases in voided volume for all five patients. CONCLUSIONS: This data provides additional evidence for the potential benefit of ABT in patients with chronic inflammatory conditions of bladder such as CRC.

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS. METHODS: Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12 weeks post-op. RESULTS: Ten females (47.4 ± 14.4 years) who had recalcitrant IC/BPS for 7.8 years (5.2-12.1 years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3 months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3 months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention. CONCLUSION: ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3 months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.

Rapid versus gradual bladder decompression in acute urinary retention.

OBJECTIVE: To demonstrate a benefit in diminished adverse events such as hypotension and hematuria with gradual drainage of the bladder when compared to rapid decompression in patients with acute urinary retention (AUR) due to benign prostatic hyperplasia in a case-control study. METHODS: Sixty-two patients matched our selection criteria presenting with AUR. They were divided into two groups - the first was managed by rapid drainage of the bladder, the second was managed by gradual drainage through a urethral catheter (The first 100 mL immediately evacuated, then the rest evacuated gradually over 2 h). RESULTS: The mean age was 64.4 and 63.2 years in the first and second group, respectively. Diagnosed cause was benign hyperplasia of the prostate. Hematuria occurred in two patients in the first group and none in the second group. The two cases of hematuria were mild and treated conservatively. After the relief of the obstruction, the mean blood pressure was noticed to decrease by 15 mmHg and 10 mmHg in the first and second group, respectively, however, no one developed significant hypotension. Pain relief was achieved after complete drainage in the first group and after the evacuation of 100 mL in the second group. CONCLUSIONS: We conclude that there is no significant difference between rapid and gradual decompression of the bladder in patients with AUR. Hematuria and hypotension may occur after rapid decompression of the obstructed urinary bladder, but these complications are rarely clinically significant.

Microbiological evaluation of infected pelvic lymphocele after robotic prostatectomy: potential predictors for culture positivity and selection of the best empirical antimicrobial therapy.

OBJECTIVES: To examine symptomatology and microbiology of infected lymphocele (LC) post-robotic-assisted radical prostatectomy and pelvic lymph node dissection (PLND) and to assess for potential predictors for LC fluid culture positivity. Secondly, to provide general recommendations about use of select antimicrobial therapy. METHODS: This was a single-center, IRB-approved, retrospective, case series review conducted between October 2008 and October 2014. Data included symptomatology, microbiology of symptomatic LC in men post-robotic prostatectomy and PLND. Those with infected LC were compared to those men with symptomatic LC in the absence of infection. RESULTS: Symptomatic LC was seen in 7% of men, and among those, infected LC was seen in 42%. Infected LC cultures showed predominance of G+ cocci such as S. aureus, coagulase-negative Staphylococcus species, S. pyogenes, S. fecalis and S. viridans. Monomicrobial infection was seen in 85%. Multivariate logistic regression showed leukocytosis [Odds: 12.3, p = 0.03, 95% CI (1.2-125)] was significant predictor for culture positivity, whereas trend toward significance for factors such CT findings of thickened walls around the LC +/- air. CONCLUSIONS: LC infection following PLND for prostate cancer is usually monomicrobial and caused by Gram+ cocci. GI tract and skin flora are the main habitat. High index of suspicion of infected LC is undertaken in the presence of leukocytosis, fever and abnormal CT findings. Based upon our local hospital antibiogram, combination of IV ampicillin/sulbactam and vancomycin is suggested as the best initial empiric therapy in treating these patients.

The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary.

OBJECTIVES: Several researchers have reported the relationship between infertility in male and varicocele for so many years but the implication of varicocele in female patients is remains elusive. Here, we aim to examine the effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality of rat ovary after the experimental creation of varicocele in female rats. MATERIALS AND METHODS: In this study, thirty adult female albino rats were divided into three equal groups: Group 1 as the control group has 10 rats, Group 2 as the sham group has 10 rats and they underwent a sham operation and finally Group 3 has the varicocele group has 10 rats. Antioxidant assays for superoxide dismutase, glutathione peroxidase and catalase were performed using specific assay kits and gene expression for Bax, Bmp-15, Hsp-27 and Gdf-9 was done via real time PCR. RESULTS: The adverse effects of the experimentally induced varicocele were reported and recorded on the left ovary compared to the right sided ovary (no varicocele induction) in the varicocele group. Real time PCR data shows that the expression of Gdf-9, Hsp-27 and Bmp-15 genes were all significantly reduced at p≤ 0.05. CONCLUSION: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female.

A unique view on male infertility around the globe.

BACKGROUND: Infertility affects an estimated 15% of couples globally, amounting to 48.5 million couples. Males are found to be solely responsible for 20-30% of infertility cases and contribute to 50% of cases overall. However, this number does not accurately represent all regions of the world. Indeed, on a global level, there is a lack of accurate statistics on rates of male infertility. Our report examines major regions of the world and reports rates of male infertility based on data on female infertility. METHODS: Our search consisted of systematic reviews, meta-analyses, and population-based studies by searching the terms "epidemiology, male infertility, and prevalence." We identified 16 articles for detailed study. We typically used the assumption that 50% of all cases of infertility are due to female factors alone, 20-30% are due to male factors alone, and the remaining 20-30% are due to a combination of male and female factors. Therefore, in regions of the world where male factor or rates of male infertility were not reported, we used this assumption to calculate general rates of male factor infertility. RESULTS: Our calculated data showed that the distribution of infertility due to male factor ranged from 20% to 70% and that the percentage of infertile men ranged from 2·5% to 12%. Infertility rates were highest in Africa and Central/Eastern Europe. Additionally, according to a variety of sources, rates of male infertility in North America, Australia, and Central and Eastern Europe varied from 4 5-6%, 9%, and 8-12%, respectively. CONCLUSION: This study demonstrates a novel and unique way to calculate the distribution of male infertility around the world. According to our results, at least 30 million men worldwide are infertile with the highest rates in Africa and Eastern Europe. Results indicate further research is needed regarding etiology and treatment, reduce stigma & cultural barriers, and establish a more precise calculation.

Engaging practicing gynecologists in the management of infertile men.

In the modern era, contemporary management of male infertility has undergone groundbreaking changes with the introduction of new concepts, advanced testing, and therapeutic interventions. As practicing gynecologists are often the first physicians who encounter an infertile couple, it is essential that these clinicians are continuously updated about the new pearls and pitfalls of male infertility management. Semen analysis is commonly ordered by gynecologists. In 2010, the WHO released new cutoff reference values for the semen parameters adopting novel methodology, which has incited much debate. Reference values have been lowered in comparison with previous standards, with a direct clinical implication in decision-making strategies. Specialized sperm-function tests, such as sperm oxidative stress and sperm chromatin integrity assessments, became clinically available, thus offering an opportunity to better understand sperm dysfunctions concealed during routine semen analysis. Furthermore, the initial counseling of azoospermic men by an andrologically well educated gynecologist may alleviate the misconception and distress surrounding the false belief of sterility, and will clarify the available options of percutaneous and microsurgical sperm-retrieval techniques and assisted conception outcome. Regarding varicocele, which is commonly seen in infertile males, it is now clear that the best treatment option for infertile men with clinical varicocele is the microsurgical vein ligation. Natural conception is significantly improved after varicocelectomy, and recent data suggest that such treatment optimizes reproductive outcome of couples undergoing ICSI or micro-TESE sperm retrieval. Lastly, new therapeutic interventions, including oral antioxidant therapy and lifestyle modifications, have gained increasing attention, as they aid in alleviating male infertility.

Early return of continence in patients undergoing robot-assisted laparoscopic prostatectomy using modified maximal urethral length preservation technique.

PURPOSE: To evaluate the impact of maximal urethral length preservation (MULP) technique in comparison with posterior urethral reconstruction and anterior bladder suspension (PRAS) technique on the continence rates (CR), time to achieve continence among patients with prostate cancer (PCa) undergoing robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: We prospectively analyzed the CR, time to achieve continence, pre- and postoperative prostate-specific antigen (PSA) levels, rates of positive margins among three groups of continent men with PCa undergoing RALP from whom consent was obtained. Each group consisted of 30 patients: PRAS was performed in group A, combined MULP and PRAS in group B, and MULP in group C. Continence was measured by patient self-reporting of the number of pads/24 h. RESULTS: No differences were detected in the age, preoperative PSA levels, biochemical recurrence, prostate volume, and positive margins for the three groups. Men in groups B and C had marked improvement in CR 1, 3, and 6 months after catheter removal vs group A (50% and 70% vs 10%, 90% and 96.66% vs 23.3% and 100%, 100% vs 53.3%, respectively, P<0.0001). The average and median times to continence were significantly shorter in group B (5.4 and 4 weeks) and C (3.8 and 3 weeks) vs group A (27.4 and 22.5 weeks), P<0.00001. Using Cox regression analysis, only MULP and MULP+PRAS techniques were significantly correlated with continence outcomes 1, 3, and 6 months after catheter removal. CONCLUSIONS: MULP rather than PRAS confers higher postoperative CR and shorter time to achieve continence among patients with PCa who underwent RALP without increasing risk of positive margin.

Proteomic analysis of human spermatozoa proteins with oxidative stress.

BACKGROUND: Oxidative stress plays a key role in the etiology of male infertility. Significant alterations in the sperm proteome are associated with poor semen quality. The aim of the present study was to examine if elevated levels of reactive oxygen species cause an alteration in the proteomic profile of spermatozoa. METHODS: This prospective study consisted of 52 subjects: 32 infertile men and 20 normal donors. Seminal ejaculates were classified as ROS+ or ROS- and evaluated for their proteomic profile. Samples were pooled and subjected to LC-MS/MS analysis through in-solution digestion of proteins for peptide characterization. The expression profile of proteins present in human spermatozoa was examined using proteomic and bioinformatic analysis to elucidate the regulatory pathways of oxidative stress. RESULTS: Of the 74 proteins identified, 10 proteins with a 2-fold difference were overexpressed and 5 were underexpressed in the ROS+ group; energy metabolism and regulation, carbohydrate metabolic processes such as gluconeogenesis and glycolysis, protein modifications and oxidative stress regulation were some of the metabolic processes affected in ROS+ group. CONCLUSIONS: We have identified proteins involved in a variety of functions associated with response and management of oxidative stress. In the present study we focused on proteins that showed a high degree of differential expression and thus, have a greater impact on the fertilizing potential of the spermatozoa. While proteomic analyses identified the potential biomarkers, further studies through Western Blot are necessary to validate the biomarker status of the proteins in pathological conditions.

A comprehensive review of genetics and genetic testing in azoospermia.

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients.

Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress.

OBJECTIVE: To identify the relative abundance of proteins in pooled reactive oxygen species (ROS)-positive (ROS+) and ROS-negative (ROS-) semen samples with the use of two-dimensional differential in-gel electrophoresis (2D-DIGE). DESIGN: Spermatozoa suspensions from ROS+ and ROS- groups by 2D-DIGE analysis. SETTING: Tertiary hospital. PATIENT(S): 20 donors and 32 infertile men. INTERVENTION(S): Seminal ejaculates evaluated for semen and proteomic analysis. MAIN OUTCOME MEASURE(S): Semen samples from 20 donors and 32 infertile men were pooled, divided into ROS+ and ROS- groups based on the cutoff value of <20 relative light units/s/10(6) sperm and frozen. From each pooled group, spermatozoa were labeled with Cy3/Cy5 fluorescent dye. Duplicate 2D-DIGE gels were run. Image analysis was performed with the use of Decider software. Protein spots exhibiting ≥1.5-fold difference in intensity were excised from the preparatory gel and identified by liquid chromatography-mass spectrometry. Data were analyzed with the use of Sequest and Blast programs. RESULT(S): A total of 1,343 protein spots in gel 1 (ROS-) and 1,265 spots in gel 2 (ROS+) were detected. The majority of protein spots had similar expression, with 31 spots were differentially expressed. Six spots were significantly decreased and 25 increased in the ROS- sample compared with the ROS+ sample. CONCLUSION(S): Significantly different expression of protective proteins against oxidative stress was found in ROS-compared with ROS+ samples. These differences may explain the role of oxidation species in the pathology of male infertility.

Insight into oxidative stress in varicocele-associated male infertility: part 2.

Varicocele, the leading cause of male infertility, can impair spermatogenesis through several pathophysiological mechanisms. Of these, current evidence suggests that oxidative stress is the central element contributing to infertility in men with varicocele, to which the testis responds by way of heat stress, ischaemia or production of vasodilators, such as nitric oxide. Surgical varicocele repair (varicocelectomy) is beneficial not only for alleviating oxidative stress-associated infertility, but also for preventing and protecting against the progressive character of varicocele and its consequent upregulations of systemic oxidative stress. However, antioxidant therapy in infertile men with surgically treated and those with untreated varicocele is poorly studied, and well-designed trials are needed.

A comprehensive review of genetics and genetic testing in azoospermia

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients.

Insight into oxidative stress in varicocele-associated male infertility: part 1.

Varicocele is recognized as the leading cause of male infertility because it can impair spermatogenesis through several distinct pathophysiological mechanisms. Current evidence supports oxidative stress as a key element in the pathophysiology of varicocele-related infertility, although these mechanisms have not yet been fully described. Measurement of the reactive oxygen species and other markers of oxidative stress, including the levels of the antioxidant enzymes catalase and superoxide dismutase, can provide valuable information on the extent of oxidative stress and might guide therapeutic management strategies. The testis can respond to varicocele-associated cell stressors, such as heat stress, ischaemia or production of vasodilators (for example, nitric oxide) at the expense of the generation of excessive reactive oxygen species. These responses have their own implications in exacerbating the underlying oxidative stress and on the subsequent infertility.

Unexplained male infertility: diagnosis and management.

Unexplained male infertility is a diagnosis reserved for men in whom routine semen analyses results are within normal values and physical as well as endocrine abnormalities were ruled out. In addition to erectile problems and coital factors, immunologic causes and sperm dysfunction may contribute to such condition. New etiologies of unexplained male infertility include low level leukocytospermia and mitochondrial DNA polymerase gene polymorphism. Contemporary andrology may reveal cellular and sub-cellular sperm dysfunctions which may explain subfertility in such cases, thus aiding the clinician to direct the further work-up, diagnosis and counseling of the infertile male. The objective of this article is to highlight the concept of unexplained male infertility and focuses on the diagnosis and treatment of this condition in the era of modern andrology and assisted reproductive techniques. Extensive literature review was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus.

Male infertility: a critical review of pharmacologic management.

INTRODUCTION: Male factor infertility contributes partially and solely to the problem of childlessness in around 50% of the cases. Unfortunately, 30 - 50% of the etiologies of male infertility are unknown and therefore, no specific therapy can be instituted. Evidence-based medical therapy for male infertility is an attractive research area where a large number of clinical trials, controlled and uncontrolled, using different types of medications have been conducted yielding variable results and outcomes. AREAS COVERED: In this review, we summarize and evaluate the most important and most recent information pertaining to the use of different medications in male infertility and assign level of evidence to these medications. An extensive literature search was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus. EXPERT OPINION: Male infertility represents a very challenging area of clinical medicine. Many different types of medications have been tried and very few have had satisfactory results. There is a huge need to advance and develop andrologic diagnostic techniques, focusing on the metabolomics and proteomics of the sperm, seminal plasma, and testicular tissue. Clarification of the causes of idiopathic male infertility and the discovery of novel molecular targets will help guide future innovative development of new pharmacologic agents.

Unexplained Male infertility: diagnosis and Management

Unexplained male infertility is a diagnosis reserved for men in whom routine semen analyses results are within normal values and physical as well as endocrine abnormalities were ruled out. In addition to erectile problems and coital factors, immunologic causes and sperm dysfunction may contribute to such condition. New etiologies of unexplained male infertility include low level leukocytospermia and mitochondrial DNA polymerase gene polymorphism. Contemporary andrology may reveal cellular and sub-cellular sperm dysfunctions which may explain subfertility in such cases, thus aiding the clinician to direct the further work-up, diagnosis and counseling of the infertile male. The objective of this article is to highlight the concept of unexplained male infertility and focuses on the diagnosis and treatment of this condition in the era of modern andrology and assisted reproductive techniques. Extensive literature review was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus.

What every gynecologist should know about male infertility: an update.

PURPOSE: Our article reviews the evolving concepts in the field of male infertility for gynecologists and other health professionals involved in the care of men and women experiencing difficulty in having a child. The increased knowledge will help in the better management and treatment of infertile couples. METHODS: Review of literature through Pubmed, Science Direct, Online Library. RESULTS: Gynecologists are often the first healthcare providers to assess an infertile couple. Because half of all infertility problems stem from male factors, it is crucial for the gynecologist to remain updated on the main conditions that cause male infertility as well as current diagnostic tools and treatment options, including conventional strategies and assisted reproductive techniques. CONCLUSIONS: Extraordinary advances have been achieved in the field of male infertility over the past several years and many old concepts are now challenged. Therefore, it is imperative that male infertility physicians should update the gynecologists about the recent advances in the work-up of infertile men in terms of diagnosis and management. Such convention will help improve the standards of care for the infertile couple and enhance the cooperation between male and female reproductive endocrinologists.